NFAT Signaling in Osteoblasts Regulates the Hematopoietic Niche in the Bone Microenvironment
Joint Authors
Sesler, Cheryl L.
Zayzafoon, Majd
Source
Clinical and Developmental Immunology
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-09-01
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Osteoblasts support hematopoietic cell development, including B lymphopoiesis.
We have previously shown that the nuclear factor of activated T cells (NFAT) negatively regulates osteoblast differentiation and bone formation.
Interestingly, in smooth muscle, NFAT has been shown to regulate the expression of vascular cellular adhesion molecule-1 (VCAM-1), a mediator of cell adhesion and signaling during leukocyte development.
To examine whether NFAT signaling in osteoblasts regulates hematopoietic development in vivo, we generated a mouse model expressing dominant-negative NFAT driven by the 2.3 kb fragment of the collagen-αI promoter to disrupt NFAT activity in osteoblasts (dnNFATOB).
Bone histomorphometry showed that dnNFATOB mice have significant increases in bone volume (44%) and mineral apposition rate (131%) and decreased trabecular thickness (18%).
In the bone microenvironment, dnNFATOB mice displayed a significant increase (87%) in Lineage−cKit+Sca-1+ (LSK) cells and significant decreases in B220+CD19−IgM− pre-pro-B cells (41%) and B220+CD19+IgM+ immature B cells (40%).
Concurrent with these findings, LSK cell differentiation into B220+ cells was inhibited when cocultured on differentiated primary osteoblasts harvested from dnNFATOB mice.
Gene expression and protein levels of VCAM-1 in osteoblasts decreased in dnNFATOB mice compared to controls.
These data suggest that osteoblast-specific NFAT activity mediates early B lymphopoiesis, possibly by regulating VCAM-1 expression on osteoblasts.
American Psychological Association (APA)
Sesler, Cheryl L.& Zayzafoon, Majd. 2013. NFAT Signaling in Osteoblasts Regulates the Hematopoietic Niche in the Bone Microenvironment. Clinical and Developmental Immunology،Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-446966
Modern Language Association (MLA)
Sesler, Cheryl L.& Zayzafoon, Majd. NFAT Signaling in Osteoblasts Regulates the Hematopoietic Niche in the Bone Microenvironment. Clinical and Developmental Immunology No. 2013 (2013), pp.1-11.
https://search.emarefa.net/detail/BIM-446966
American Medical Association (AMA)
Sesler, Cheryl L.& Zayzafoon, Majd. NFAT Signaling in Osteoblasts Regulates the Hematopoietic Niche in the Bone Microenvironment. Clinical and Developmental Immunology. 2013. Vol. 2013, no. 2013, pp.1-11.
https://search.emarefa.net/detail/BIM-446966
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-446966